Kristian G. AndersenGeverifieerd account

This project started when docs John Bradley & @Lauge_Farnaes from @radychildrens contacted me about a suspected outbreak of non-vaccine type H. influenzae: 2 kids with severe meningitis within 1 week in the same hospital, where no H. flu patients had been seen for years. 1/nhttps://twitter.com/biorxiv_micrbio/status/1125109731851481088 …

First question: was this the beginning of an outbreak? Genomics says no. We sequenced an isolate from each kid (H1 and H2) and placed them in a H. flu phylogeny. H1 and H2 clearly belong to distantly related lineages. 2/n

NB: we had this result, confidently excluding a recent transmission chain and local outbreak, within about 2 weeks including sample shipping, DNA extraction, MiSeq, and phylogenetics. However it took us 3 years to write up the paper... 3/n

Second question: H1 and H2 are distantly related, but do they share particular genes that allowed them both to emerge at the same place & time? Well, they both encode a type-a capsule, which allows them to avoid the vaccine (which targets type-b). 4/n

H1 & H2 also share near-identical sequence in part of the capsule locus, suggesting a recombination event between recent ancestors of H1 and H2, probably within the past decade in North America. So, recombination of the capsule locus could help H. flu evade vaccines. 5/n

The capsule locus is a hotspot of recombination & diversifying selection in pneumococcus, Klebsiella, and other pathogens (as shown by @RafalMostowy @KelWyres & others) and the same may well be true (but under-appreciated) in Haemophilus influenzae. 6/n

Last fun tidbit: H1 and H2 come from distinct lineages, but these lineages appear to have a preference to exchange genes with one another. Unclear why, but perhaps an overlapping niche... 7/n

This work was a labour of love by star research scientist Yves Terrat (not on twitter) and @NTromas who did the sequencing back in 2016 ! 8/8